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Updated: Jun 15, 2026
05:52
Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality
Sumin Han1, Museer A Lone, Roger Schneiter
1Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Summary
Yeast Orm proteins regulate lipid homeostasis and protein quality control. Their absence disrupts sphingolipid synthesis, leading to endoplasmic reticulum stress and impaired cell growth.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Yeast Orm proteins (Orm1 and Orm2) are endoplasmic reticulum (ER) membrane proteins crucial for cellular lipid balance.
- Dysregulation of lipid homeostasis can impact protein quality control and cellular stress responses.
Purpose of the Study:
- To investigate the role of yeast Orm proteins in regulating lipid homeostasis and its connection to protein quality control.
- To elucidate the impact of Orm protein deficiency on sphingolipid and phospholipid metabolism.
- To understand the underlying mechanisms of cellular dysfunction in yeast lacking Orm1 and Orm2.
Main Methods:
- Genetic analysis of yeast strains lacking Orm1 and Orm2 (orm1Δorm2Δ).
- Biochemical assays to measure lipid levels, including sphingolipid precursors.
- Analysis of gene expression related to phospholipid biosynthesis.
- Assessment of cellular phenotypes such as growth, stress sensitivity, and protein transport.
Main Results:
- Absence of Orm1 and Orm2 leads to accumulation of long chain base, indicating disrupted sphingolipid synthesis.
- Orm proteins physically interact with serine palmitoyltransferase, a key enzyme in sphingolipid synthesis.
- orm1Δorm2Δ cells exhibit inositol auxotrophy and impaired transcriptional regulation of phospholipid biosynthesis genes.
- Deficiency in Orm proteins results in constitutive unfolded protein response, stress sensitivity, and delayed ER-to-Golgi transport.
- Inhibiting sphingolipid synthesis alleviates the growth defects and ER stress in orm1Δorm2Δ cells.
Conclusions:
- Yeast Orm proteins are critical regulators of both sphingolipid and phospholipid homeostasis.
- Disrupted lipid homeostasis due to Orm protein absence directly contributes to ER stress and impaired cellular functions.
- Yeast Orm proteins coordinate lipid metabolism with protein quality control to maintain membrane biogenesis and cellular health.
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